Professional Documents
Culture Documents
March 2019;62(1):17-23
DOI: 10.5281/zenodo.2590001
UDC: 616.24-002.5(478)
1
Department of General Hygiene, 2Department of Pneumophtisiology, 3Department of Morphopathology
Nicolae Testemitsanu State University of Medicine and Pharmacy Chisinau, the Republic of Moldova
Corresponding author: evelinalesnic@yahoo.com
Manuscript received January 23, 2019; revised manuscript March 01, 2019
Abstract
Material and methods: A retrospective selective, descriptive study of socioeconomic, epidemiological peculiarities, case-management, diagnosis and
microbiological characteristics of 694 patients with tuberculosis registered in Chisinau in 2016 was performed. Among them 581, had an urban residency
and 112 rural residency.
Results: Residents from rural population and young persons in urban areas were most affected. Socioeconomic vulnerability predominated in both
subpopulations; however, the gravity was more represented in the urban group. Lower level of education and tuberculosis contacts were more dominating
in the rural group. Comorbidities, HIV infection were more frequently identified in the urban group, but destructive forms – in the rural patients. Low
treatment outcomes were more frequently established in the rural group.
Conclusions: Risk factors for tuberculosis in urban subpopulation were: unemployment, lack of health insurance, homelessness, comorbidities, HIV
infection. In rural population prevailed the following risk factors: low school education and tuberculosis contact.
Key words: tuberculosis, risk factors, outcome.
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A. Tihon et al. Moldovan Medical Journal. March 2019;62(1):17-23 ORIGINAL ARTICLE
average density of the rural population being 7 inhabitants/ and high risk habits associated with the alcohol and
km2 [5]. tobacco consumption and unhealthy diet [16, 17]. The
The regional system of the RM was founded on the basis poor management of the healthcare, human resources, a
of legislative acts: the law of the regional development no. big distance between the villages and primary health care
438-XVI of 28.12.2006, the National Strategy for Regional institutions multiplied the barriers for the accessibility of
Development (decision no 158 of 04.03.2010) and the the rural population to low price healthcare services [9, 14,
regulatory framework that establishes the institutions which 18, 19, 20]. Enumerated conditions aggravated by the social,
are responsible for the regional development (decision no economical vulnerability contributed to the extension of the
127 of 08.02.2008) [6, 7]. The regional development of the tuberculosis in the rural population.
RM is realized according to the regional policy that aims So, the aim of the study was to assess the tuberculosis
to perform the territorial cohesion, which means to reduce features and risk factors of patients, residents of the urban
the gaps between urban and rural localities, between the sectors and rural localities of Chisinau city.
center and the periphery of the RM [7]. Assessing the health Objectives were: 1. Assessment of the socioeconomic
care disparities it was established that the rural households and epidemiological risk factors of patients with tuber-
spent for health more than the urban family groups: 5.9% culosis and comparing them according to the urban and
vs. 5.4% in 2014, 6.6% vs. 6.5% in 2015 from the total family rural residence. 2. Evaluation of the case-management,
income [8]. It is one of the major indices that showed a diagnosis type, radiological aspects and microbiological
reduced accessibility for public health services of the rural characteristics of tuberculosis patients and comparing them
population [9]. The poverty rate in rural areas is 5 times according to the urban and rural residence. 3. Identification
higher than in urban areas [8]. It was found that 86% of the of the risk factors for tuberculosis, according to the urban
poorest people from the RM live in villages [10]. Several and rural residence.
social categories are among the poorest persons: families
which are dependent only on agricultural activities, families Results and discussion
with a lot of children, the elderly, persons with low levels According to the data obtained from the monitoring
of education attainment and lack of professional skills [11]. and follow-up of the case system during the period of 2016
Distributing the population, according to the area of were registered 694 tuberculosis cases among all residents
their habitation (house) it was established that in urban of Chisinau, which included 581 patients from the urban
localities one person possesses 19.4 meters2 and in rural sectors and 112 from rural communes: Bacioi, Bic, Braila
areas – 23 meters2/person [12]. Even if the area of the rural (Bacioi), Bubuieci, Budesti, Tohatin, Cruzesti, Ciorescu,
household is larger per capita, the quality and endowment Codru, Colonita, Singera, Ghidighici, Stauceni, Gratiesti,
are below the basic needs, which include electricity, natural Truseni, Vadul lui Voda and Vatra [12].
gas, heating system, safe water and sewerage, as well the While distributing selected patients, according to the sex
telecommunication (phone line) [12]. The urban areas have it was established the statistical predominance of men, with
a better developed infrastructure, but the rural areas have an the highest rate in the rural group. So, men were 82 (73.2%)
inhomogeneous distribution of the basic needs. All exposed in the rural group and 392 (67.5%) in the urban group with
data demonstrated the cause of the discrepancy of the public a male/female ratio 2.1/1 in the urban group and 2.3/1 in
health indicators between urban and rural localities. While the rural group. Repartition of the patients into age groups,
analyzing the statistical reports were established multiple according to the WHO recommendation identified that the
healthcare problems and socially determined morbidities largest subgroup in the urban group was between 25 and
in rural localities: malnutrition, hipovitaminosis, severe 34 years old – 136 (23.4%) patients, followed by those who
anemia, tuberculosis, scabies, pediculosis. [14]. Residents of were between 35 and 44 years old – 125 (21.5%) patients,
rural communities are more exposed to polluted water and between 45 and 54 years old – 115 (19.7%) patients and
to the consumption of dangerous food, due to the infestation between 55 and 64 years old – 100 (17.2%) patients. In a
of the land with wastewater and pesticides [13]. Current minor proportion were represented patients younger than
researches demonstrated a high level of the rural residents 24 years old – 41 (7.1%) cases.
poisoning by poor management of the pesticides, fungicides, In the rural group predominated patients who were
herbicides and insecticides. Due to the unequal distribution between 35 and 44 years – 33 (29.4%) patients, followed by
of the natural gas system, the residents of rural areas of the those who were between 45 and 54 years – 23 (20.5%), also
RM use fossil fuels (wood, coal and oil derivatives), which between 55 and 64 years – 22 (19.6%) patients. In a minor
increase the risk of indoor air pollution with toxic gases such proportion of patients were included young groups, who
as carbon monoxide and other combustion gases involving were between 25 and 34 years old – 19 (16.9%) and younger
the risk of involuntary poisoning and death [14]. than 24 years – 10 (8.9%) cases. While comparing the groups
Current political and economic trends are based on was identified the predominance of the young subgroup
the reduction of the accessibility to the public healthcare of 25-34 years old in the urban group compared with the
services and increasing of the private sector offers [15]. rural group: 136 (23.4%) vs. 19 (16.9%) patients, and older
A significant proportion of people from rural localities adults in the rural compared with the urban group: between
have no compulsory insurance policy, lack of education 35 and 44 years old – 33 (29.4%) vs. 125 (21.5%) patients,
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ORIGINAL ARTICLE A. Tihon et al. Moldovan Medical Journal. March 2019;62(1):17-23
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A. Tihon et al. Moldovan Medical Journal. March 2019;62(1):17-23 ORIGINAL ARTICLE
as chronic alcoholism predominated in the urban group – 10 (8.9%) cases. Pulmonologists detected more frequently
54 (9.2%) vs. 6 (5.4%), as well as the drug use – 10 (1.7%) symptomatic patients from the urban group – 146 (25.1%)
vs. 1 (0.9%) patients in the rural group, as well as mental vs. 21 (18.7%). It is the consequence of the lack of the
disorders – 11 (1.8%) vs. 1 (0.9%) case. Chronic respiratory specialized medical staff, which manages the patients from
and gastrointestinal diseases (including hepatitis) diseases the rural localities. High risk groups screening performed
predominated in the urban group – 37 (6.4%) vs. 6 (5.4%) by pulmonologists detected more frequently patients from
and respectively 51 (8.7%) vs. 5 (4.4%) cases. No other the rural group – 10 (8.9%) vs. 33 (5.6%) cases. Directly
statistical differences were detected among groups regarding for hospitalization into a specialized institution came more
the associated diseases (Table 4). frequently urban residents – 158 (27.1%) vs. 26 (23.2%)
While distributing patients, according to the registered patients from the rural localities. So, it can be deducted that
type of case it was identified that new cases predominated in specialized hospital is more accessible for urban residents
the rural group – 70 (82) vs. 355 (61.1%) patients in the ur- than for rural people. Death cases were more frequently
ban group. Each fourth patient in every group had a relapse detected in tuberculosis people from the rural localities –
– 137 (23.6%) patients in the urban group and 28 (25%) 5 (4%) than from urban districts of Chisinau – 12 (2%).
patients in the rural group. At a similar rate were patients Information is exposed in the table 5.
included in the treatment after a previous “lost to follow- Table 5
up” – 12 (10.7%) patients in the urban vs. 57 (9.8%) patients
Case-management characteristics
in the rural group and after a “treatment failure” – 29 (4.9%)
of tuberculosis patients
patients in the urban vs. 2 (1.8%) patients in the rural group.
Diagnosed and transferred from abroad to the RM were 3 Urban Rural
(0.5%) patients. Data were demonstrated in the table 4. group group P
Health level Detection ways
N=581 N=112 value
Table 4 (P%) (P%)
PHC Detected by GPs 181 (31.1) 45 (40.1) >0.05
Distribution according to the risk groups
symptomatics
Urban Rural Detected by GPs 63 (10.8) 10 (8.9) >0.05
group group P screening of HRG
Category Risks factors
N=581 N=112 value Ambulatory Detected by SP 146 (25.1) 21 (18.7) >0.05
(P%) (P%) specialized symptomatics
Socioeco- Poverty 165 (28.4) 36 (32.1) >0.05 level Detected by SP 33 (5.6) 10 (8.9) >0.05
nomic Homelessness 130 (22.4) 17 (15.2) <0.05 screening of HRG
Migration 59 (10) 11 (9.8) >0.05 Hospital level Direct addressing 158 (27.1) 26 (23.2) >0.05
History of detention 33 (5.8) 5 (4.5) >0.05
Biological Close contact 38 (6.5) 16 (14.3) <0.05 Others Postmortem 12 (2) 5 (4) >0.05
Associated diseases 258 (44.4) 24 (21.4) <0.001 Note: Applied statistical test: paired simple T-test, P – probability;
HIV-infection 59 (10.1) 3 (2.6) <0.001 GP-general practitioner, SP-specialist, HRG-high risk group.
Diabetes 10 (1.7) 1 (0.9) >0.05
Chronic alcoholism 54 (9.2) 6 (5.4) >0.05
Identifying the clinical, radiological forms of pulmonary
CRD 37 (6.4) 6 (5.4) >0.05
tuberculosis it was established that pulmonary tuberculo-
GID 51 (8.7) 5 (4.4) >0.05
sis was diagnosed in a similar proportion in both groups –
Mental disorders 11 (1.8) 1 (0,9) >0.05
546 (93.9%) vs 106 (94.6%) patients, as to extrapulmonary
(excluding IVDU)
forms of tuberculosis – 31 (5.4%) vs. 6 (5.4%) patients.
Neoplasm 7 (1.2) 0 >0.05
Generalized tuberculosis was established only in the urban
Renal diseases 5 (0.8) 1 (0.9) >0.05
group – 4 (0.6%) patients. Pulmonary infiltrative tuberculo-
Immune suppressive 3 (0.5) 0 >0.05
sis was identified in a similar proportion in both groups –
treatment
495 (85.2%) in the urban group vs. 97 (91.6%) patients in
Drug users 10 (1.7) 1 (0.9) >0.05
the rural group. Disseminated pulmonary tuberculosis was
Others 12 (2.0) 0 >0.05
established more frequently in the rural group – 5 (4.7%) vs
Note: Applied statistical test: paired simple T-test, P – probability; 18 (3.3%) patients from the urban group. Destructive forms
NA-non available, CRD-chronic respiratory diseases, GID-gastrointestinal
diseases.
of pulmonary tuberculosis were identified in a higher pro-
portion in both groups, however, the destructive process
in both lungs was statistically more frequently identified in
Studying case-management, it was identified that the
the rural group – 36 (32.1%) vs. 97 (16.9%) patients (tab. 6).
general medical staff was involved in the detection of most
When assessing the laboratory features of the enrolled
of the patients from the both groups and more perceptibly
pulmonary tuberculosis patients, it was identified that one
in the rural group – 45 (40.1%) vs 181 (31.1%) patients
third of the entire sample was microscopic positive for acid-
from the urban group. Screening of the people with high
fast-bacilli, 162 (27.8%) patients in the urban vs. 38 (33.9%)
risk performed by the general practitioners detected more
patients in the rural group. A similar proportion of pa-
frequently patients from the urban group – 63 (10.8%) vs.
tients was identified to have positive bacteriological results
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ORIGINAL ARTICLE A. Tihon et al. Moldovan Medical Journal. March 2019;62(1):17-23
Table 6
Microbiological features of tuberculosis patients
Urban group Rural group
Index Radiological features P value
N=581 (P%) N=112 (P%)
Clinical forms of TB Pulmonary TB 546 (93.9) 106 (94.6) >0.05
Extrapulmonary 31 (5.4) 6 (5.4) >0.05
Generalized 4 (0.6) 0 >0.05
Clinical forms PIT 495 (85.2) 97 (91.6) >0.05
of pulmonary TB PDT 18 (3.3) 5 (4.7) >0.05
FCVT 33 (6.1) 4 (3.7) >0.05
Localization of destruction One lung 171 (29.4) 38 (33.9) >0.05
Both lungs 97 (16.9) 36 (32.1) <0.001
Microbiological features AFB positive 162 (27.8) 38 (33.9) >0.05
MBT culture positive 155 (26.7) 35 (31.2) >0.05
GeneXpert MTB positive 227 (39.1) 51 (45.4) >0.05
GeneXpert MTB/Rif sensible 142 (24.4) 17 (15.2) <0.05
GeneXpert MTB/Rif resistent 85 (14.6) 34 (30.4) <0.01
MBT culture positive AFB positive 97 (16.6) 26 (23.2) >0.05
MBT culture positive AFB positive GeneXpert positive 81 (13.9) 23 (20.5) >0.05
MDR-TB 51 (8.8) 13 (11.6) >0.05
Note: Applied statistical test: paired simple T-test, P – probability; PIT-pulmonary infiltrative tuberculosis, PDT-pulmonary disseminated tuberculosis,
FCVT-fibro-cavernous tuberculosis. Applied statistical test: paired simple T-test, P – probability.
at cultivation on solid Lowenstein-Jensen or liquid MGIT The standard treatment for drug susceptible tuberculosis
BACTEC media: 155 (26.7%) patients in the urban vs. 35 was used for the treatment of a similar proportion of
(31.2%) patients in the rural group. The molecular genetic patients from both groups: 530 (91.2%) patients from the
assay was performed in all cases, but positive results were urban group and respectively 99 (88.4%) patients from
obtained more frequently in the rural group – 51 (45.4%) vs. the rural group. Every third patient from the urban group
227 (39.1%) patients in the urban due to a high proportion and every fifth patient from the rural group was treated as
of cases with destructive forms of tuberculosis. Sensitive to previously treated cases – 226 (38.9%) patients from the
rifampicin were more frequently identified patients from the urban group and 60 (37.5%) patients from the rural group.
rural group – 142 (24.4%) vs. 17 (15.2%), however, resistant Even the rate of MDR-TB was in average similar in both
to rifampicin have been more frequent cases in the rural groups, only a minor proportion of patients from both
group – 34 (30.4%) vs. 85 (14.6%) cases in the urban group. groups was treated as drug-resistant patients: 51 (8.8%)
Microscopically positive for AFB and cultivation on the patients from the urban group and 13 (11.6%) patients
conventional media proved to be Mycobacterium tuberculo- from the rural group. It is important to emphasize that the
sis (MTB) more frequently in the rural group – 26 (23.2%) standard treatment for MDR-TB could be started only if the
vs. 97 (16.6%) in the urban group, as well microscopic posi- therapeutic compliance of the patient is established and the
tive for AFB, culture positive for MTB and GeneXpert MTB clinical tolerance is acceptable (tab. 7).
Rif positive assay were 23 (20.5%) patients from rural group
Table 7
vs. 81 (13.9%) patients from the urban group.
The standard treatment for new drug-susceptible tuber- Types of the cases according to the history
culosis in the RM has been used since 2000, lasts 6 months of the anti-tuberculosis treatment
and consists of two phases with four first-line drugs: isoniazid Case type Outcome Urban Rural P
(H), rifampicin (R), ethambutol (E) and pyrazinamide (Z) group group value
in the intensive phase and two first-line drugs: isoniazid N=581 N=112
and rifampicin in the continuation phase. For previously (P%) (P%)
treated cases was used a regimen which lasts 8 months: 3 Never treated New case 355 (61.1) 70 (62.5) >0.05
months with H, R, E, Z and streptomycin and 5 months with before
H, R and E. Patients with rifampicin-resistance or MDR-TB Previously Relapse 137 (23.6) 28 (25) >0.05
were treated with second-line drugs for 18 months or more treated Recovered after 57 (9.8) 12 (10.7) >0.05
divided in two phases. The regimen composition during default
the intensive phase lasts 6 months and includes kanamycin Recovered after 29 (4.9) 2 (1.8) <0.05
(Km) or capreomycin (Cm), levofloxacin (Lfx), para-amino failure
salicylic acid (PAS), ethionamide (Eto), cycloserine (Cs) Types of the First-line anti-TB 530 (91.2) 99 (88.4) >0.05
and pyrazinamide (Z) and for continuation phases during drugs drugs
12-18 months – Lfx, PAS, Etho, Cs and Z. Second-line anti-TB 51 (8.8) 13 (11.6) >0.05
drugs
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A. Tihon et al. Moldovan Medical Journal. March 2019;62(1):17-23 ORIGINAL ARTICLE
All the patients were managed and treated with the stan- as a hallmark of the late detection of tuberculosis process.
dard treatment for tuberculosis. First-line anti-tuberculosis When leveling the risk factors it was established that more
drugs were used in 531 (91.4%) patients from urban group relevant was the tuberculosis contact followed by the low
vs. 13 (11.7%) patients from the rural group. Successfully level of education (tab. 9).
treated were more frequently patients in the rural group – The relation between tuberculosis indices and demo-
80 (71.4%) vs. 373 (64.2%) patients in the urban group. The graphic particularities was widely studied [24, 25, 26, 27, 11,
low therapeutic outcome was more frequently established in 28]. Globally, the epidemics of tuberculosis is much higher
the urban group, such as “lost to follow-up” – 45 (7.7%) vs. in urban areas than in rural localitites, because almost one
5 (4.5%) cases in the rural group, died – 69 (11.9%) vs. 10 half of the world’s population lives in cities [29, 25, 26]. Our
(8.9%) patients in the rural group. Still continuing the treat- research identified high indices of tuberculosis in the ru-
ment was almost each tenth patient in both groups (tab. 8). ral subpopulation than in urban areas. It can be explained
by the complexity of risk factors, which reflects the barri-
Table 8 ers for accessing the healthcare services of the rural popula-
Treatment outcome of tuberculosis patients tion [30, 31, 32]. Several studies identified a poor quality of
healthcare in private system which manages patients with
Outcome Urban group Rural group P value
tuberculosis [33, 26, 34]. In the RM the specialized institu-
N=581 (P%) N=112 (P%)
tions offer a standard approach, which corresponds to the
Treatment success 373 (64.2) 80 (71.4) >0.05
international recommendations and national regulations
Treatment failure 9 (1.5) 0 >0.05
[35, 21, 36]. The uncontrolled urbanisation is associated
Lost to follow-up 45 (7.7) 5 (4.5) >0.05 with extension of drug resistance and poor treatment out-
Death 69 (11.9) 10 (8.9) >0.05 come [37, 38, 39]. Our research established more increased
Still continuing 63 (10.8) 10 (8.9) >0.05 rate of the drug resistance in the rural population. It can be
explained by a deeper investigation of tuberculosis contacts
Diagnosed excluded 22 (3.8) 6 (5.4) >0.05
in the rural areas. The uncontrolled urbanization is associa-
Note: Applied statistical test: paired simple T-test, P – probability. ted with lack of healthcare service at low price and expan-
sion of the private sector [26, 27]. Our research established
An important research outcome represents the odds that the major proportion of patients was detected by public
ratio (OR) and the attributable risk (AR), which are indices general practitioners and every fifth patient came directly to
for identifying the priority interventions in the frame of the hospital. No similar studies were conducted in the RM.
high risk groups from every type of the subpopulation Urbanization is associated with overcrowding, low level of
[22]. The values were calculated represented only for risk sanitation and low socioeconomic state [40, 32, 41]. Our re-
factors which predominated and exposed a statistical search identified also an important proportion of patients
difference between the groups. It was established that the from both subpopulations, which were unemployed, home-
risk factors for tuberculosis in urban patients were linked less and without health insurance, however, their amount
with the sociovulnerability: unemployment, associated lack was more prevalent in the urban group which constituted
of health insurance, homelessness or lack of the residence risk factors.
visa, comorbidities and the immune suppressive condition
– HIV infection. Attributable risk revealed the hierarchy of Conclusions
risks in urban population: HIV infection, comorbidities, Residents from the rural localities were more affected by
homelessness, lack of health insurance and unemployment. tuberculosis compared with the urban population.
In rural population the risk factors for tuberculosis were The age for acquiring tuberculosis was younger in urban
low level of the school education and tuberculosis contact. population than in that from rural areas.
Related to this was identified lung destruction in both lungs, Socioeconomic vulnerability was extended in all patients
Table 9
with tuberculosis; however, the gravity was more evident in
patients from the urban districts of Chisinau.
Risk factors for tuberculosis Low level of education predominated in the patients
AR from rural localities.
Risk factors OR
(%) Close contact with a sick patient predominated in the
Social Unemployment 1.63 (1,07-2,48) 18 patients with tuberculosis from rural localities, which
economical Lack of insurance 1.56 (1,03-2,35) 18 contributed to a higher rate of MDR-TB.
features Homelessness 1.61(0,928-2,794) 31 Associated diseases predominated in the urban group,
Low secondary education 2.06 (1,27-3,35) 17 more expressed was HIV infection.
Epidemio- Close contact 2.32 (1,27-4,44) 57 Risk factors for tuberculosis in urban population were:
logical and Associated diseases 2.9 (1,81-4,73) 52 unemployment and associated lack of health insurance,
comorbidties HIV-infection 4.1 (1,26-13,4) 80 patient’s homeless state, comorbidities and the immune
Disease Both lungs involvement 2.36 (1,5-3,71) 52 suppressive condition – HIV infection. Risk factors for the
related rural population were tuberculosis contact and low level of
Note: OR – odds ratio; AR – attributable risk. the education.
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ORIGINAL ARTICLE A. Tihon et al. Moldovan Medical Journal. March 2019;62(1):17-23
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